This application is intended to develop the career of Kevin L. Winthrop M.D., M.P.H., and in doing so, create a research program dedicated to improving drug safety and preventing serious infectious morbidity in persons with chronic inflammatory disorders like rheumatoid arthritis. Dr. Winthrop's immediate career goal is to answer key questions regarding infections that occur with novel, biologic immunosuppressant therapies called anti-tumor necrosis factor-alpha (anti-TNF) agents. His pilot project will use large, health plan databases and nested case-control techniques to evaluate the risks, types, and outcomes of mycobacterial infections in patients using these compounds. He will seek to define whether there are safety differences between the various anti-TNF agents, and whether screening for tuberculosis is associated with preventing disease. His study will not only provide important public health information, but will provide Dr. Winthrop an opportunity to learn how to design, analyze, and perform large, population-based observational studies. During the 5 year career development period, he will acquire formal training in pharmacoepidemiology, cohort study methods, as well as immunology. At the end of the five year career development period, Dr. Winthrop should be an established, independent investigator capable of conducting pharmacovigilance and other studies that identify mechanisms to decrease infectious morbidity in patients treated with biologic therapies. Relevance: This study will examine the safety of new biologic immunosuppressive therapies (called "anti-tumor necrosis factor-alpha agents") used to treat rheumatoid arthritis and other auto-immune conditions. This will be the first population-based study in the United States to evaluate the risks and factors associated with tuberculosis and related mycobacterial infections in these patients. The results will assist public health officials and clinicians to define ways to prevent these infections in patients using these popular therapies.